TOXICOLOGY

TOXICOLOGY

Study of toxic drugs or poisons

- Effects and properties of poison

- Isolation and identification of poison

- Action of poisons to living tissue

- Determination of lethal dose

- Determination of antidotes (ang tambal)

● CBC

● Urinalysis - most of this toxicity will affect the kidney

● Blood-Urine Nitrogen (in relation to the kidney)

● Electrolyte analysis

● Blood gas together with the toxic substance that is measured

In cases of drug overdose, aside from the testing for the presence of

that specific drug in the system, e-apil pud ug test si:

Toxicology

- The study of the adverse effect of xenobiotics to

the human body

Xenobiotics

substances that are foreign to the body such as

poisons, toxins, toxic drugs (antibiotics)

50%

EXPOSURE TO TOXINS

- intentional/suicide (ginusto)

30%

EXPOSURE TO TOXINS

accidental

20%

EXPOSURE TO TOXINS

- homicide/occupational (from work)

Ingestion

ROUTE OF EXPOSURE

- swallowing of substance through the mouth and

into the stomach.

- Generally followed by its entrance into the small

intestine

Inhalation

ROUTE OF EXPOSURE

- breathing causes us to inhale substances which in

return travel enroute to the lungs.

- Our lungs are so rich in blood vessels that any

substance inhaled into the lungs are readily

absorbed into the bloodstream

Transdermal

absorption

ROUTE OF EXPOSURE

- entering the body through the skin.

- Substances that absorb through the skin

sometimes further assimilate into the blood

system

Ingestion/Inhalation

ROUTE OF EXPOSURE

Aside from that, the most common route of exposure

pass the cellular barrier

ROUTE OF EXPOSURE

○ If maingest siya goes to the GI tract and passively diffuse into the

circulation kay maabsorb siya sa intestine. Because these toxins are

able to _____________.

produce

systemic effects

ROUTE OF EXPOSURE

In the circulation, it will then ___________. It can go to any organ (it could affect your heart,

liver, kidney).

produce local effect such as diarrhea,

bleeding, malabsorption of nutrients if dili muagi sa GIT.

ROUTE OF EXPOSURE

○ If inhaled or transdermal absorption, it will not produce systemic

effect instead it will only ________________

Mechanistic

BRANCHES OF TOXICOLOGY

- cellular, molecular, and biochemical effect of

xenobiotics within the context of dose response

relationship (the higher dose = the more toxic)

that will assess potential toxicity of new

chemicals

Descriptive

BRANCHES OF TOXICOLOGY

it will describe or compare risk assessment of

toxicity test

Regulatory

BRANCHES OF TOXICOLOGY

- it will formulate regulatory policies to protect

humans (more on government side)

Forensic

BRANCHES OF TOXICOLOGY

- deals with kanang mga namatay, tanawon kung

suicide ba or homicide. Pwede iexamine ang

corpses.

Clinical

BRANCHES OF TOXICOLOGY

It will study the relationship between the

xenobiotic and the disease

Environmental

BRANCHES OF TOXICOLOGY

- deals with the sources of the toxin, transport,

transformation of the toxin and how human will

be able to come in contact with these toxins

Acute Toxicity

TERMINOLOGIES

- there is a single short-term exposure to a

substance.

- Once or short-term lang siya na expose sa

substance

Chronic

Toxicity

TERMINOLOGIES

- repeated exposure for an extended period of

time

𝑇𝐷50

- TD=Toxic Dose

TERMINOLOGIES

- This is the dose that will predict when mag

produce ug toxic response in half of the

population, meaning 50% of the population

𝐿𝐷50

- LD= Lethal Dose

TERMINOLOGIES

- this is the dose that will predict the dose that will

have a lethal effect on the 50% of the population

● Lethal means death

𝐸𝐷50

- ED = Effective Dose

TERMINOLOGIES

- This is the dose that will predict an effective or

therapeutic dose to the 50% of the population

METHODS OF DETERMINATION

- Immunoassay (katong mga EMIT mao to sila ang mga common)

- Chromatographic Techniques

TLC

- Thin-layer Chromatography

METHODS OF DETERMINATION

- limited sensitivity, results must be confirmed with

another method

HPLC

METHODS OF DETERMINATION

- High Performance Liquid Chromatography

GC-MS

Gas Chromatography-Mass Spectrometry

METHODS OF DETERMINATION

-

- highly sensitive, reference method

- Alcohol

- Carbon Monoxide

- Cyanide

- Metals

- Drugs of Abuse

TOXIC AGENTS

ALCOHOL

Major substance abuse problem

Ethanol

ALCOHOL

Principle

pharmacologic

function

- CNS depressant

- Increases heart rate and blood

pressure

Ethanol Effects

ALCOHOL

- Skill thought/attention

diminishes

- Ability to hear and see

decreases

- Time perception is distorted

- Speed of moving objects is

distorted

○ That’s why bawal mag drive

while you are intoxicated with

alcohol

Ethanol Metabolism

ALCOHOL

Absorbed in the GI tract

Absorbed by inhalation of vapors

90%-98%

MAJOR ROUTES OF ETHANOL DISPOSAL

- converted by the liver

(elevation of liver enzymes)

0.5%-1.5%

MAJOR ROUTES OF ETHANOL DISPOSAL

- Perspiration and respiration

with the lung

Remainder

MAJOR ROUTES OF ETHANOL DISPOSAL

- excreted by the kidney

- Serum because it reflects the

concentration of ethanol in the

brain

- When we collect test, do not

use alcohol as disinfectant

MAJOR ROUTES OF ETHANOL DISPOSAL

Sample

Methanol

ALCOHOL

Major components of paints, varnishes, and paint

removers

- Ingestion leads to formation of formaldehyde and

formic acid

○ Common sa street kids nga nay ginasimhot

Isopropanol

ALCOHOL

- Twice the CNS depressant as ethanol but not as

toxic as methanol

- ________is converted to acetone by the ADH

Rubbing alcohol

ALCOHOL

Isopropanol Common form

CARBON MONOXIDE

- is a colorless, odorless, tasteless gas.

- Very very toxic substance

- Product of incomplete combustion of carbon containing substances

- Binds to HEME PROTEINS

CARBON MONOXIDE

Mechanism of

action

Hemoglobin

CARBON MONOXIDE

Mechanism of

action

- it will compete with bindings

sites with oxygen

Cytochrome

CARBON MONOXIDE

Mechanism of

action

inhibit cellular respiration and

electron transport

20% CO

CARBON MONOXIDE Toxic Level

Brain and Heart

CARBON MONOXIDE Susceptible organs

100% oxygen

CARBON MONOXIDE Antidote

- Whole Blood using EDTA

CARBON MONOXIDE Sample used

Cherry red color of the face

CARBON MONOXIDE Indication of

acute toxicity

oxygen bind with the

hemoglobin in the RBCs

CARBON MONOXIDE

○ In the hemoglobin, ang mu attach is the ________________.

carbon monoxide will bind with the

hemoglobin very tightly

CARBON MONOXIDE

○ In the case of carbon monoxide__________________________, so instead na oxygen ang mu bind, it’s the

carbon monoxide.

hypoxia

CARBON MONOXIDE

What will happen is that it will result to_________ since low naman

ang oxygen na madeliver to the cells and tissues

inhibit cellular respiration

also inhibit

electron transport

CARBON MONOXIDE

Kung sa cytochrome, the same mechanism with the myoglobin. It

will _______________ at the same time, it will ___________ si carbon monoxide the same with cyanide.

CYANIDE

- Super toxic substance

● it is fast acting meaning kung ma expose ka, it could result to

death in an hour

- Component of insecticides, rodenticide

- It’s a common suicidal agent

solid, a gas, or in solution.

CYANIDE

can exist either as_____________

Burning of plastic

CYANIDE

● ______________ can also result to cyanide gas.

binding to the iron-containing

substances in the body. (e.g, hemoglobin, cytochrome)

CYANIDE

It expresses its toxicity by_____________________

cellular or tissue hypoxia

CYANIDE

if mu bind siya with the iron in the hemoglobin and

cytochrome, it will lead to ____________. Kay ma

replace napud again si oxygen, and mainhibit again ang

cellular and electron transport

formation of ATP

CYANIDE

It will also prevent__________ for energy

- inhalation, ingestion, and transdermal absorption

CYANIDE

Exposure

- Odor of bitter almonds in the breath, altered mental

status

CYANIDE

Indication

of Toxicity

2 – Strep strategy

CYANIDE

Antidotes

- Oxidants (amyl nitrite and

sodium nitrite)

- Sodium thiosulfate

Hydroxocobalamin

CYANIDE

Antidotes

most common because it’s

just one step

○ Siya ang mubind kay cyanide

para dili maka bind sa

cytochrome

cytochrome a3

CYANIDE

When cyanide reaches the cells, it binds with ___________,a

subunit of the cytochrome oxidase complex.

blocking the oxygen and preventing the cell from being able

to use it.

CYANIDE ○ Effect:

Hydroxocobalamin

CYANIDE

○ __________ binds with cyanide to form nonotoxic

cyanocobalamin, which is then excreted in the urine.

large quantities

METALS

- All metals can be toxic if ingested in ____________

Mercury

METALS

- Elemental, mercurous, mercuric and alkyl

mercury

- _______ has this unique ability of being able to

amalgam (able to mix or merge with other

substances

- Considered to be potent enzyme inhibitor

- Inhibit catecholamines

inhalation, ingestion,

cutaneous, tattoo, dental

amalgams (inhale or absorb, it

could pass thru the

Blood-brain barrier)

Mercury

Exposures

- Binds to sulfhydryl group of

protein

Mercury

Mechanism of

action:

Blood or urine (24hr

Mercury Sample

- Gastric lavage

○ Ipasuka or e cleanse ang

stomach

Mercury Antidote

Reinsch Test

Mercury Method of Testing

Blood-brain barrier

Central Nervous System

Mercury

Remember that if mainhale or maabsorb nimo

siya through the skin, it could pass thru the

_________which is delikado, pwede siya

moaccumulate in the _________

loss of glomerular integrity

Mercury

○ Also, the presence of mercury in the blood may

result to_________________ which is sa

kidney nimo

Elemental

mercury

Mercury Type

- pink disease

Alkyl mercury

Mercury Type

Minamata disease

Arsenic

METALS

- Found in pesticides, weed killer and some paints

- Component of ant poison, rodenticides, pain and

metal alloys

- Inorganic (Soil & Sediments in the Water), organic

and arsine gas

- Binds to the sulfhydryl group

of Hgb (able to cross the

placental, maka adto sa fetus)

ARSENIC MECHANISM OF ACTION

INGESTATION, INHALATION

ARSENIC EXPOSURE

- Blood and urine

○ Both are for short term

assessment, acute toxicity

○ For long term: hair and nails

(exhibit lines)

ARSENIC SPECIMEN

- British Anti-Lewisite (BAL)

○ it will trigger extreme vomiting

ARSENIC ANTIDOTE

odor of garlic, metallic taste in

the mouth

ARSENIC INDICATION OF TOXICITY

- Reinsch Test,

- Atomic Absorption

Spectroscopy (AAS)

ARSENIC METHOD OF TESTING

Lead

METALS

- nafamous due to news about toys from a certain

country contains a _______ in their paint

- Paint/ Soil/Gasoline

- Attach to RBC

- Aminolevulinic Acid (ALA)

LEAD POTENT ENYME INHIBITOR

● the first compound in

the Porphyrin

Synthesis (which is ang

mu lead sa Heme

- Respiratory (Inhalation)

- GI (Ingestion)

LEAD EXPOSURE

Child/Adult

LEAD SYMPTOMS

Venous Blood;EDTA

LEAD SPECIMEN

- Basophilic Stippling, ALA and

Porphyrin in the urine

LEAD INDICATON OF TOXICITY

Cadmium

METAL

- Manufacture of batteries, metal plating, plastic

● Pwede nimo maingest si ____________ if imong

food is acidic and you placed it in a metal

nga balonan that contains _____________

- Higher in females due to differences in iron stores

● There is increased _________ for those who

are Iron Deficient

- Inhalation (damage the lungs)

- ingested (damage the tubules

of the kidneys)

CADMIUM EXPOSURE TYPE

● damage to the Type 1

Epithelial Cells in your

lungs and madecrease

ang bacterial

resistance to

BINDS TO RBC

CADMIUM MECHANISM OF ACTION

URINE AND WHOLE BLOOD

CADMIUM SPECIMEN

PROTEINURIA

CADMIUM INDICATION

Amine derivatives with Benzine Ring

- Most all Drugs of Abuse are __________________,

and most of this DOA, ilang effect is in the neurotransmitter system;

ila awat-awaton si Dopamine

Amphetamines

DRUGS OF ABUSE

- Used therapeutically for Narcolepsy and ADHD;

Gina abuse lang and some kay modified form

which is called DESIGNER DRUG

- E.g., Ecstacy (MDMA), (MDEA)

- Effect: cause the release of dopamine from the

brain leading to a pleasant feeling

- Upon testing of ___________ like sa Drug

Screening, if nag drink ug antihistamine si

patient it could lead to false-positive reaction.

Anabolic

Steroids

DRUGS OF ABUSE

- Chemically related to testosterone because

these are performance enhancing drugs.

- Bawal ni siya because it will improve the athletic

performance of an athlete by increasing the

muscle mass

Cannabinoids

(Marijuana)

DRUGS OF ABUSE

- Naturally occurring _________ which is found

in the plant; Cannabis sativa;

- Hallucinogen – cause hallucinations

- Detected in the urine within 3-5 days; if chronic

user, 4 weeks